STUDY PROCEDURES. Detailed descriptions of patient evaluations required for this protocol are described in this section. These evaluations will be performed during the indicated times, days, and weeks of the study described in Section 8 and the Schedule of Events tables in Appendix 1 (Cohorts 1-3) and Appendix 2 (Cohort 4). All data collected are to be recorded on the appropriate eCRF. Additional details for study procedures, including sample collection, are described in the Manual of Operations or Laboratory Manual as appropriate for this study. 7.1 Informed Consent Prior to conducting any study-related procedures, written informed consent must be obtained from the patient’s parent(s) or legally authorized representative(s) and assent from the patient (if applicable). At a minimum, the date of the initial consent will be captured on the eCRF. The nature, scope, and possible consequences, including risks and benefits, of the study will be explained to the patient, the patient’s parent(s), or the patient’s legally authorized representative by the Investigator or designee in accordance with the guidelines described in Section 11.4.Documentation of the consent process and filing of informed consent documents should be completed according to Section 11.4. 7.2 Inclusion/Exclusion Criteria At Screening, each patient will be reviewed for eligibility against the study entrance criteria. Patients who do not continue to meet the study entrance criteria will not be allowed to participate in the study. The reason(s) for the patient’s ineligibility for the study will be documented. Refer to the eCRF Completion Manual for additional instructions for patient screen failures. 7.3 Confirmation of Study Eligibility and MLD Diagnosis and Genotype Cohorts 1-3:Patient eligibility according to the study inclusion and exclusion criteria will be assessed during the Screening period. Sites will be allowed one opportunity to re-screen any patient who fails initial screening or withdraws consent prior to device implantation). If the patient subsequently screen fails, the patient will no longer be considered for inclusion in the study. Assays for leukocyte arylsulfatase A enzyme activity, urine sulfatide, and genotype determination will be performed by specialty laboratory(ies) designated by Shire to confirm the diagnosis of MLD.5, 30 Biochemical confirmation of MLD diagnosis is required for study eligibility, but genotype results are not. Local leukocyte arylsulfatase A enzyme activity and urine sulf...
